摘要:

Short stature and excess weight in adulthood are both associated with an increased risk of health problems. In a population-based investigation, data on birth length, birth weight, and gestational age for males born in Sweden in 1976 were used to predict the risk of being short or overweight in adulthood. The Swedish Birth Register was used to identify singleton males, born to Nordic mothers, who were without malformations and alive at 18 y of age. After individual record linkage between the Birth Register and the Swedish Conscript Register, information about height and weight at 18–21 y was obtained for 90% (n= 39 901) of the birth cohort. Logistic regression analyses were used to estimate the risk of being short or overweight at conscription. The odds ratio (OR) was used to estimate relative risk. At conscription, mean height (±SD) was 179.5 ± 6.6 cm, mean weight 72.1 ± 11.2 kg, and mean body mass index 22.3 ± 3.1 kg/m2. The risk of short adult stature (<166.3 cm) was associated with being short for gestational age (OR = 5.9), having a low birth weight for gestational age (OR = 1.7), and being born at a gestational age below 32 wk (OR = 2.6). The risk of being overweight (body mass index > +2 SD) was primarily associated with a high ponderal index (> +2 SD; OR = 1.8). In conclusion, anthropometric birth data are better predictors of short stature than of being overweight in adulthood. Among anthropometric data at birth, birth length is the most important predictor of adult height.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

To investigate the gonadal control of FSH secretion in prepuberty, we studied the relationship between circulating inhibin B and FSH levels in 16 prepubertal boys with cryptorchidism (age range, 1–8 y). The effect of Leydig cell stimulation on the secretion of inhibin B, sex steroids, and FSH was investigated in nine boys who were given human chorionic gonadotropin (hCG) treatment. In these boys, serum inhibin B, testosterone, estradiol, and gonadotropin levels were measured before and on the fourth day of the last (third) hCG injection, given at 1-wk intervals. Except for one boy with both high inhibin B and FSH concentrations, basal serum levels of these hormones correlated negatively (rS= −0.79,n= 15,p< 0.005). This inverse relationship remained significant in the subgroup of boys younger than 2 y of age (rS= −0.84,n= 11,p= 0.008) who also had greater variance of serum FSH concentrations than 14 control boys of similar age with normally located testes (p< 0.01). hCG stimulation increased serum testosterone and suppressed serum FSH concentrations in each boy (n= 9,p< 0.005). In the four oldest subjects, the serum inhibin B level increased from the mean of 91 to 135 pg/mL (p< 0.05). These findings suggest that inhibin B regulates FSH secretion in early childhood. Moreover, the hCG-induced suppression of FSH secretion was probably mediated by sex steroids rather than by inhibin B. Finally, the increase in serum inhibin B concentration during the hCG treatment was likely to be indirect via Leydig cell-Sertoli cell or Sertoli cell-germ cell interaction(s).

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

&agr;-Mannosidosis is a lysosomal storage disorder resulting from deficient activity of lysosomal &agr;-mannosidase. It has been described previously in humans, cattle, and cats, and is characterized in all of these species principally by neuronal storage leading to progressive mental deterioration. Two guinea pigs with stunted growth, progressive mental dullness, behavioral abnormalities, and abnormal posture and gait, showed a deficiency of acidic &agr;-mannosidase activity in leukocytes, plasma, fibroblasts, and whole liver extracts. Fractionation of liver demonstrated a deficiency of lysosomal (acidic) &agr;-mannosidase activity. Thin layer chromatography of urine and tissue extracts confirmed the diagnosis by demonstrating a pattern of excreted and stored oligosaccharides almost identical to that of urine from a human &agr;-mannosidosis patient. Widespread neuronal vacuolation was observed throughout the CNS, including the cerebral cortex, hippocampus, thalamus, cerebellum, midbrain, pons, medulla, and the dorsal and ventral horns of the spinal cord. Lysosomal vacuolation also occurred in many other visceral tissues and was particularly severe in pancreas, thyroid, epididymis, and peripheral ganglion. Axonal spheroids were observed in some brain regions, but gliosis and demyelination were not observed. Ultrastructurally, most vacuoles in both the CNS and visceral tissues were lucent or contained fine fibrillar or flocculent material. Rare large neurons in the cerebral cortex contained fine membranous structures. Skeletal abnormalities were very mild. &agr;-Mannosidosis in the guinea pig closely resembles the human disease and will provide a convenient model for investigation of new therapeutic strategies for neuronal storage diseases, such as enzyme replacement and gene replacement therapies.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We report the first case of maternal uniparental disomy for chromosome 6 (UPD6mat) ascertained through congenital adrenal hyperplasia (CAH), which arose because of reduction to homozygosity of an autosomal recessive mutation. This case suggests that UPD6mat is associated with intrauterine growth retardation (IUGR). A case of paternal UPD (involving only the short arm of chromosome 6) ascertained as CAH has previously been reported, but was not stated to have IUGR. Our patient was born with IUGR followed by extraordinarily good catch-up growth. She had a history of a marked lag in motor development. She presented at 2.65 y of age with pubarche of 3 mo duration, clitoral enlargement, and an advanced bone age. Simple virilizing CAH was diagnosed by elevations of plasma 17-hydroxyprogesterone and testosterone. Mutation analysis showed that the CAH was due to homozygosity for the I172N exon 4 mutation. When parental DNA was examined, the mother was found to be heterozygous for the uncommon exon 4 mutation, while the father had no detectable mutations. DNA microsatellite analysis was subsequently performed on the patient and parents using polymorphic markers spanning the entire chromosome 6. Seven markers were informative for inheritance of a single maternal allele and absence of paternal alleles in the proband. Analysis of microsatellite markers from other chromosomes confirmed biparental inheritance at these loci. This combination of findings is diagnostic of UPD6mat. The only other reported case of UPD6mat was discovered serendipitously when genotyped for renal transplantation; this patient had a history of IUGR. Since both cases of UPD6mat had IUGR, the phenotype appears to include IUGR as well as the potential to unmask an autosomal recessive trait.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The effects of blocking endothelin (ET) receptors in pulmonary circulation during hypoxemia and reoxygenation were studied in five groups of piglets. Ten minutes before hypoxemia, the Hyp group (n= 10) was given saline and the 1-mg (n= 9) and 5-mg group (n= 9), respectively, were given 1 and 5 mg/kg i.v. SB 217242 (an ET receptor antagonist). Two groups served as normoxic controls. The piglets were ventilated with 8% O2until base excess was <−20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with air. The increase of mean pulmonary artery pressure was significantly attenuated during hypoxemia and reoxygenation in the 1-mg group (p= 0.006). The pulmonary vascular resistance index increased significantly at the end of hypoxemia in the Hyp and 5-mg groups but was comparable to baseline in the 1-mg group. During the study period, the changes in pulmonary vascular resistance index were significantly attenuated in the 1-mg group compared with the 5-mg group. Stroke volume index was significantly attenuated compared with baseline in the 5-mg group during both hypoxemia and reoxygenation, whereas, in the Hyp and 1-mg group, stroke volume index was attenuated only at the end of hypoxemia. During hypoxemia, plasma ET-1 decreased from 1.9 ± 0.2 to 1.3 ± 0.3 ng/L (p= 0.008) in the Hyp group, remained unchanged in the 1-mg group, and increased from 1.6 ± 0.2 to 6.6 ± 1.6 ng/L (p= 0.008) in the 5-mg group. We conclude that blocking ET receptors attenuates pulmonary vasoconstriction during hypoxemia and reoxygenation in piglets.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

During fetal life, the pulmonary epithelium secretes liquid that distends the airways and is important for normal lung growth and development. The factors regulating human fetal lung liquid secretion are poorly understood; however, recent studies in murine models show that keratinocyte growth factor (KGF, FGF-7) and fibroblast growth factor 10 (FGF-10) stimulate liquid secretion. We asked whether KGF and FGF-10 stimulate liquid secretion in human fetal lung. First trimester fetal lung explants developed dose-dependent increases in intraluminal volume in response to KGF and FGF-10. Although there were no acute changes in explant transepithelial potential difference in response to KGF (0.1–1000 ng/mL), exposure to 5–50 ng/mL KGF over 60 h depolarized transepithelial potential difference compared with controls. We used ribonuclease protection assays to quantitate the ontogeny and regulation of mRNA expression for KGF and its receptor. Both mRNA were expressed in fetal and postnatal lung. Because the promoter region of the human KGF gene contains cAMP and IL-6 response elements, we asked whether cAMP or IL-6 stimulated expression of KGF or its receptor. We have previously shown that cAMP stimulates liquid secretion in this model. Both cAMP and IL-6 significantly increased expression of KGF but not KGF receptor during a 48-h experiment. Thus, stimulation of liquid secretion in explant models by cAMP may be mediated in part by induction of KGF expression. KGF and FGF-10 may be important paracrine factors regulating liquid secretion in human fetal lung.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

To determine the role of surfactant protein B (SP-B) in bacterial clearance from the airways, three groups of mice expressing different levels of SP-B were studied: wild-type mice, hemizygous SP-B mice, and SP-B overexpressing transgenic mice. SP-B levels in overexpressing mice were increased 5-fold relative to hemizygous mice and 2- to 3-fold over wild-type littermates. Mice from each group were infected intratracheally with the common airway pathogens, group B streptococci orPseudomonas aeruginosa. There was no significant difference in the number of recoverable viable bacteria at 6 h (group B streptococci andP. aeruginosa) and at 24 h (P. aeruginosa) among the three groups. Similarly, systemic dissemination of bacteria was not different among the three groups for both pathogens and at both time points. We conclude that SP-B levelsin vivodo not influence clearance of bacteria from the lungs.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Normal control of breathing is characterized by maintenance of CO2and O2arterial pressures at constant levels by appropriate ventilatory responses to changes in CO2production and O2consumption. Abnormal development of this regulatory system during embryogenesis may produce early impairments in chemosensitivity, as in congenital central hypoventilation syndrome. The present study addresses the role of the mammalian achaete-scute homologous gene (Mash-1) in the development of respiratory control. We analyzed ventilatory responses to hypercapnia (8% CO2, 21% O2, 71% N2) and hypoxia (10% O2, 3% CO2, 87% N2) in newborn and adultMash-1heterozygous mice (Mash-1+/−) and their wild-type littermates (Mash-1+/+). Ventilation, breath duration, and tidal volume were measured using whole-body plethysmography. Ventilatory responses to hypercapnia were significantly weaker in newborn maleMash-1+/−compared withMash-1+/+mice as a result of a weaker breath-duration response. No differences were observed between adultMash-1+/−andMash-1+/+mice. Our data suggest thatMash-1may be involved in respiratory control development via mechanisms linked to the X chromosome.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

We previously reported that erythropoietin (Epo) is present in human cerebrospinal fluid (CSF). It is not known whether CSF Epo concentrations change under conditions of CNS injury or, if so, whether this change reflects loss of blood-brain barrier integrity or increased CNS Epo synthesis. We hypothesized that CSF Epo increases in conditions of neural injury including hypoxia, meningitis, and intraventricular hemorrhage (IVH) and that CSF Epo concentrations are independent of plasma Epo concentrations. To test these hypotheses, Epo concentrations were measured in 122 paired CSF and blood samples obtained from neonates and children categorized as follows: 16, asphyxia; 31, meningitis; 11, IVH; 41, controls. Twelve infants treated with recombinant Epo (rEpo) and 11 additional samples from children with miscellaneous neurologic problems were also evaluated. CSF and plasma Epo concentrations were significantly higher in asphyxiated infants than in controls (225.0 ± 155.0versus4.5 ± 0.5 mU/mL; mean ± SEM,p< 0.05, respectively, in CSF; 1806.7 ± 1254versus5.2 ± 0.5,p< 0.05 in plasma). Neonates with IVH had higher CSF Epo concentrations than controls (p< 0.01) but did not have higher plasma Epo concentrations than controls. Patients with meningitis did not have elevated CSF or plasma Epo concentrations. There was no correlation between CSF and plasma Epo concentrations in infants treated with rEpo. We conclude that Epo is selectively increased in the CSF by hypoxia, less so by IVH, and not at all by meningitis. rEpo treatment does not elevate CSF Epo. These findings suggest that rEpo does not cross the blood-brain barrier and that hypoxia induces increased CNS synthesis of Epo.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Inherited thrombocytopenias are a heterogenous group of disorders. Different criteria have been suggested to classify the forms, such as the inheritance mechanism and the platelet volume as well as the number and morphology of megakaryocytes. However, the classification is often descriptive, and the precise mechanism of thrombocytopenia still remains unknown. We describe the clinical, biologic, and molecular findings of an autosomal dominant thrombocytopenia in a large family. The 17 patients had normocellular bone marrow and normal platelet volume. Platelets also showed a normal aggregation test and normal response to ADP and thrombopoietin (TPO). In the affected subjects, the mean ± SD levels of platelet count and plasma TPO were 62 ± 25 and 258 ± 151, respectively. Comparative analysis showed that the patients with platelet count <70 000 had higher plasma TPO concentration. The data are consistent with a mild clinical form of the disease associated with only a few episodes of bleeding. To exclude the possible role of TPO and its receptor c-mpl in the etiology of this condition, linkage analysis was performed using microsatellite markers close to theTPOandc-mplgenes on chromosomes 3q26.3-q27 and 1p34, respectively. The absence of cosegregation within the affected family indicated that these genes, as well as two other candidate loci on chromosomes 11 and 21, are not responsible for this hereditary dominant form of thrombocytopenia. A genome-wide search and subsequent identification of the gene will provide new insight into the pathogenesis of this disorder.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID